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Photosensitivity and Pain in Traumatic Brain InjuryNadir Balba, PhD Candidate
mTBI Symposium
12/13/2019
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TBI and Chronic Pain• Chronic pain is a common complaint from individuals with TBI (Nampiaparampil, 2008)
• Can occur in individuals 10+ years our from initially head injury
r = 0.41
RP
Q (
Sco
re)
Pain (Score)
TBI Severity vs Pain
Adapted from Balba & Elliott et al., 2018
P <0.0001
n = 337
Pain Complaints
***
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• Chronic pain often explained by “central sensitization”: heightened activity in pain-processing circuits at the spinal cord and in brain
• Responsible for allodynia and hyperalgesia
• Direct demonstration of central sensitization difficult in patients
Central Sensitization
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Martenson et al., 2016
A Link between Light and Pain• In rodent models, light can activate nociceptive neurons while simultaneously inhibiting anti-nociceptive neurons
• Patients with fibromyalgia report higher levels of photosensitivity, light can activate pain-related circuitry in these subjects
Harte et al., 2016
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Photosensitivity and Pain in TBI• Photosensitivity is a common symptom after TBI and can last for years after injury
(Callahan et al., 2016; Balba et al., 2018)
• Photosensitivity complaints are correlated with pain complaints
n =111
Adapted from Balba & Elliott et al., 2018
Photo
sensi
tivit
y (
Sco
re)
Self-reported Photosensitivity Score
***
0 2 4 6 8 100
2
4
6Pain vs Photosensitivity
Pain (Score)
Photo
sensitiv
ity (
Score
)P
hoto
sensi
tivit
y (
Sco
re)
Pain (Score)
Pain vs Photosensitivity
r = 0.51
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Rationale for Current Study
n =111
1. Test photosensitivity and pain thresholds using more objective measures in TBI subjects, with and without symptoms, and non-TBI subjects
2. Determine whether photosensitivity is related to clinical pain complaints and whether light can activate pain-related circuitry in TBI subjects suffering from chronic pain
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Verriotto et al., 2017
0.00
100.00
200.00
300.00
400.00
500.00
600.00
700.00
800.00
Trials
Methods• Quantify visual photosensitivity thresholds (VPT) using Ocular Photosensitivity
Analyzer
• Provides a continuous variable of photosensitivity using objective stimuli
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Clauw et al., 1999
Methods• Quantify pressure pain thresholds and tolerance levels using pressure algometry
• Correlates with pain complaints in other chronic pain populations
• Has been gold standard in pain research
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Differences in Self-Reported Chronic Pain
Chronic Pain Impact Score
SIQ
R S
co
re
***
Mic
hig
an
Pain
Map
Sco
re
Degree of Widespread Pain
***
(N = 113)
(N =107)
(N =135)
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No Differences in Pressure Algometry
Pressure Threshold Levels
kP
a
Pressure Tolerance Levels
kP
a
(N = 113)
(N =107)
(N =135)
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Strong Correlation between VPT and Chronic Pain
Lu
x (
log
10)
SIQR Score
VPT vs Chronic Pain ScoresVPT Levels
Lu
x (
log
10
)
***
(N = 113)
(N =107)
(N =135)
r = -0.40; p <0.001
r = -0.34; p = 0.001
r = -0.36; p <0.001
All subjectsr = -0.51; p <0.001
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A Marker in Chronically Symptomatic TBI• Symptomatic TBI group exhibit higher levels of chronic pain, sleep disturbances
depression, PTSD symptoms, and disability than asymptomatic and non-TBI groups
Photosensitivity
Chronic Pain
Sleep
Disturbances
Disability
PTSD
SymptomsDepression
Pressure
Tolerance
Pressure
Threshold
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Conclusions
• Photosensitivity could be used as a marker of central sensitization in “high-impact” chronic pain populations• These populations are often treated with ineffective opioid medications, this novel
marker could inform new treatment options
• Future Directions:• Currently collecting fMRI data to test whether light is activating pain-related
circuitry in out symptomatic TBI population• Longitudinal studies that track the progression of photosensitivity following TBI• Continuing rodent studies to better understand neural circuitry
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Portland VA/OHSU:
Mary Heinricher, PhD
Miranda Lim, MD, PhD
Jonathan Elliott, PhD
Carolyn Jones, PhD
Kris Weymann, PhD, RN
Peyton Wickham, BSc
Alisha McBride, BSc
Randall Olson, BA
Nadir Balba, MS
Cadence Michel, BA
Kate Gutowsky, BA
Current support: NIH TL1TR002371 (NMB)
DoD PH-TBI Award W81XWH-17-1- 0423 (MMH &MML)
RRD SPiRE and Merit Award (MML)
NIH BUILD EXITO Institutional Core
Portland VA Research Foundation
OHSU Medical Research Foundation
Collaborators:
Matt Butler, PhD
Scott Mist, PhD
Kim Jones, PhD
Binyam Nardos, PhD
Megan Callahan, PsyD
Acknowledgments
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Links Between Light and Pain
On-Cell
Heat Reflex
Off-Cell
Heat Reflex
Neutral Cell
Heat Reflex
• The rostral ventromedial medulla (RVM) is key brain region encoding painful
stimuli
• Electrophysiological recordings have characterized 3 types of neurons, 2 of
which are responsive to painful stimuli
• ON-cells
• OFF-cells
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• Response linked to intrinsic photosensitive retinal ganglion cells (ipRGCs)
• Encode environmental light levels through their activity
• Part of non-image forming vision
• Project to the olivary pretectal nucleus (OPt)
• When OPt is blocked, ON/OFF cells no longer respond to light
POOPt
Trigeminal Ganglion
Links Between Light and Pain
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***
“Triple (+) diagnosis” group reports more symptomatic
TBI than all other groups (P <0.001)
Self-report,
Chart, or
HTEC interview
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ROC by Evaluation Congruency
• Number of positive diagnoses
has a significant effect on
accuracy of model:• Triple (+) had significantly
higher AUC than Single (+) or
Double (+).
• Single (+) and Double (+)
were no better than chance!
• TBI status is predicted by NSI
scores only in Triple (+)
subjects.
AUC=0.51; 95% CI [0.49, 0.61]; P <0.001 AUC=0.76; 95% CI [0.68, 0.84]
AUC=0.59; 95% CI [0.40, 0.61]; P = 0.01
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(Moulton, 2009)
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VPT vs Threshold
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VPT vs Tolerance
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Tolerance vs SIQR
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Threshold vs SIQR
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VPT vs SIQR